The Value of Female Animal Models in Drug Abuse Research// Spring 2020
With cocaine usage steadily increasing throughout the country, the need for research to better understand why some demographics are more vulnerable to drug abuse has also risen. By labs such as Dr. Michael Nader’s team at Wake Forest School of Medicine, it has been seen that a wide range of variables, including gender, may have an influence on the likelihood of addiction after exposure.
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“There’s data to suggest that even though males abuse drugs at a higher rate than females, females are more vulnerable, and they will progress to addiction faster,” says Ben Johnson, a research associate at Dr. Nader’s lab.
However, finding women to study the changes that occur within the brain before and after cocaine addiction is rather difficult. Instead, data is collected using models with similar brains, bodies, and social behaviors.
The source of this data? Monkeys. Research animal models, such as those used in Dr. Nader’s lab, can inform us about drug abuse behaviors in humans due to their similar brains, social behaviors, and hormone production.
“Their social hierarchies are an excellent model of the human condition, and they of course have a complex behavioral repertoire you can study,” says Dr. Nader. These behaviors, if need be, can include introducing monkeys to cocaine.
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Through increasing the amount of dopamine moving throughout the brain, cocaine is able to produce addictive levels of rewarding and pleasurable feelings. This increase, however, does not come without a price; Usage has been seen to alter the availability of D2 receptors, or places that are activated by dopamine.
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In Dr. Nader’s study, male monkeys were analyzed to determine whether their social status would affect changes in D2 receptor availability and vulnerability to cocaine. It was seen that the dominant, more popular males had a greater increase in D2 receptors available. When given the choice between cocaine or food, the lower-ranked males were more prone to choose cocaine. When running the same analysis with females, it would be intuitive to think that the dominant females would respond in the same way as the dominant males.
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However, this wasn’t the case. Although the dominant female monkeys, like the dominant males, had an increase in D2 receptor availability, they were much more vulnerable to cocaine use than the lower-ranked monkeys.
“It’s the exact opposite. The dominant female monkeys acquired cocaine at significantly lower doses, the exact opposite of what we saw in the males,” Dr. Nader said. “In terms of [determining] vulnerability, the strategies are different.”
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Despite a conclusion suggesting differences in vulnerabilities between genders, there is little drug abuse research conducted on female animal models. Within neuroscience research, a study found that approximately 5 males animals are used for every female animal. In the studies that reported gender, only 20% studied both sexes.
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“[These studies] are basically saying, ‘I’m going to study 50% [of the population] and call it good’,” says Johnson.
Encouragement to include female animals within neuroscience research is relatively new; it wasn’t until 2014 that the National Institute of Health (NIH) announced a policy that required labs to report their plans to eventually have both genders included within their studies. This, among several other policies, was adopted with hopes to encourage animal models that may better represent all genders.
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Despite policy amendments, underlying complications have delayed the inclusion of female animals in studies. As stated by Dr. Wayne Pratt, a psychology professor at Wake Forest, in a tongue-in-cheek manner, “Women are complicated.”
Potential disturbances due to menstruation and the impact that the varying levels of hormones may have on the data has limited the amount of research conducted in the past. For labs such as Dr. Pratt’s research that looks at dopamine and its reward system, these complications add another variable that might decrease the accuracy of the results.
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“To really study females well and understand their behavior, one would need to test females at all the stages of their estrous [hormone] cycle,” says Dr. Pratt. “An experiment that might take 8 male rats to complete might require many more females to capture their behavioral patterns across multiple stages of estrous.”
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There is hope by some, such as Nina Norman, a research technician at Dr. Nader’s lab, that more research will be conducted despite the additional time and resources that may be needed when studying female models. Results like Dr. Nader’s that highlights the sex differences in vulnerability to cocaine addiction may provide this encouragement.
“The more we talk about [research on female models], the more we try to emphasize its importance,” says Norman. “And the more we show data behind sex differences in general, the more powerful it becomes.”
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Word Count: 770
Reporting Index:
Michael Nader PhD., Professor of Physiology and Pharmacology
Ben Johnson, Research Associate
Nina Norman, Research Technician
Wayne Pratt PhD., Professor of Psychology
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